1. Field of the Invention
This invention pertains to new adenosine A3 receptor antagonists and methods of their use.
2. Description of Related Art
Adenosine exerts a number of physiological functions through activation of four cell membrane receptors classified as A1, A2A, A2B and A3. The most recently discovered subtype, the A3 subtype, has been the subject of intensive pharmacological characterization. Although all adenosine subclasses belong to the G protein-coupled receptors they are associated with different second messenger systems. The A3 subtype is believed to have a characteristic second messenger profile, in that it has been shown to mediate adenylyl cyclase inhibition and phospholipase C activation.
The adenosine A3 receptor is also believed to play a role in modulation of cerebral ischemia, inflammation, ischemic heart pre-conditioning and asthma. Thus, A3 receptor agonists find use in the treatment of these diseases. The A3 receptor is also a therapeutic target on cell growth, on apoptosis, on leukemic Jurkat T cells, on the human malignant melanoma A375 cell line and on human neutrophils. The human cloned A3 adenosine receptor was first characterized with N6-(4-amino-3-[125I]iodobenzyl)adenosine.